Epidemiological studies demonstrated that the number of emergency-room visits for respiratory indications increases during periods of Florida Red Tides. The purpose of this study was to examine whether or not repeated
brevetoxin inhalation, as may occur during a Florida Red Tide, affects pulmonary responses to
influenza A. Male F344 rats were divided into four groups: (1)
sham aerosol/no
influenza; (2)
sham aerosol/
influenza; (3)
brevetoxin/no
influenza; and (4)
brevetoxin/
influenza. Animals were exposed by nose-only inhalation to vehicle or 50 μg
brevetoxin-3/m3, 2 h/d for 12 d. On d 6 of
aerosol exposure, groups 2 and 4 were administered 10,000 plaque-forming units of
influenza A, strain HKX-31 (H3N2), by intratracheal instillation. Subgroups were euthanized at 2, 4, and 7 d post
influenza treatment. Lungs were evaluated for viral load,
cytokine content, and histopathologic changes. Influenza virus was cleared from the lungs over the 7-d period; however, there was significantly more virus remaining in the group 4 lungs compared to group 2. Influenza virus significantly increased interleukins-1α and -6 and
monocyte chemotactic protein-1 in lung;
brevetoxin exposure significantly enhanced the
influenza-induced response. At 7 d, the severity of perivascular and peribronchiolar inflammatory cell infiltrates was greatest in group 4.
Bronchiolitis persisted, with low incidence and severity, only in group 4 at d 7. These results suggest that repeated inhalation exposure to
brevetoxin may delay virus particle clearance and recovery from
influenza A
infection in the rat lung.